中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2400094049
最近更新日期： Date of Last Refreshed on：	2024-12-16 17:14:28
注册时间： Date of Registration：	2024-12-16 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	冻干结核病mRNA疫苗（RH119）在健康成年受试者中的安全性和免疫原性临床研究
Public title：	Clinical Study on Safety and Immunogenicity of lyophilized tuberculosis mRNA Vaccine (RH119) in Healthy Adult Subjects
注册题目简写：
English Acronym：
研究课题的正式科学名称：	冻干结核病mRNA疫苗（RH119）在健康成年受试者中的安全性和免疫原性临床研究
Scientific title：	Clinical Study on Safety and Immunogenicity of lyophilized tuberculosis mRNA Vaccine (RH119) in Healthy Adult Subjects
研究课题代号(代码)： Study subject ID：
在二级注册机构或其它机构的注册号： The registration number of the Partner Registry or other register：

申请注册联系人：	聂琦	研究负责人：	黄朝林
Applicant：	Qi Nie	Study leader：	Chaolin Huang
申请注册联系人电话： Applicant telephone：	+86 139 9567 6217	研究负责人电话： Study leader's telephone：	+86 153 0717 3189
申请注册联系人传真： Applicant Fax：		研究负责人传真： Study leader's fax：
申请注册联系人电子邮件： Applicant E-mail：	whsjytyy_gcp@163.com	研究负责人电子邮件： Study leader's E-mail：	whsjytyy_gcp@163.com
申请单位网址(自愿提供)： Applicant website(voluntary supply)：		研究负责人网址(自愿提供)： Study leader's website(voluntary supply)：
申请注册联系人通讯地址：	湖北省武汉市东西湖区银潭路1号	研究负责人通讯地址：	湖北省武汉市东西湖区银潭路1号
Applicant address：	No.1 Yintan Road, Dongxihu District, Wuhan City, Hubei Province	Study leader's address：	No.1 Yintan Road, Dongxihu District, Wuhan City, Hubei Province
申请注册联系人邮政编码： Applicant postcode：	420023	研究负责人邮政编码： Study leader's postcode：	420023
申请人所在单位：	武汉市金银潭医院(武汉市传染病医院)
Applicant's institution：	Wuhan Jinyintan Hospital (Wuhan Infectious Disease Hospital)
研究负责人所在单位：	武汉市金银潭医院(武汉市传染病医院)
Affiliation of the Leader：	Wuhan Jinyintan Hospital (Wuhan Infectious Disease Hospital)

是否获伦理委员会批准：	是
Approved by ethic committee：	Yes
伦理委员会批件文号： Approved No. of ethic committee：	KY-2024-21.02	伦理委员会批件附件： Approved file of Ethical Committee：	查看附件View
批准本研究的伦理委员会名称：	武汉市传染病医院医学伦理委员会
Name of the ethic committee：	Wuhan Infectious Disease Hospital Medical Ethics Committee
伦理委员会批准日期： Date of approved by ethic committee：	2024-11-25 00:00:00
伦理委员会联系人：	阮姝楠
Contact Name of the ethic committee：	Shunan Ruan
伦理委员会联系地址：	湖北省武汉市东西湖区银潭路1号
Contact Address of the ethic committee：	No.1 Yintan Road, Dongxihu District, Wuhan City, Hubei Province
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 27 8550 9839	伦理委员会联系人邮箱： Contact email of the ethic committee：	whsjytyy_ec@163.com

研究实施负责（组长）单位：

武汉市金银潭医院(武汉市传染病医院)

Primary sponsor：

Wuhan Jinyintan Hospital (Wuhan Infectious Disease Hospital)

研究实施负责（组长）单位地址：

湖北省武汉市东西湖区银潭路1号

Primary sponsor's address：

No.1 Yintan Road, Dongxihu District, Wuhan City, Hubei Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	湖北	市(区县)：
Country：	China	Province：	Hubei	City：
单位(医院)：	武汉市金银潭医院(武汉市传染病医院)	具体地址：	湖北省武汉市东西湖区银潭路1号
Institution hospital：	Wuhan Jinyintan Hospital (Wuhan Infectious Disease Hospital)	Address：	No.1 Yintan Road, Dongxihu District, Wuhan City, Hubei Province

经费或物资来源：

武汉瑞佶生物科技有限公司

Source(s) of funding：

Wuhan Ruiji Biotechnology Co., Ltd

研究疾病：

结核病

Target disease：

tuberculosis

研究疾病代码：

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

探索性研究/预试验

Study phase：

0

研究设计：

随机平行对照

Study design：

Parallel

研究目的：

主要目的：评价 RH119 在健康成年受试者中的安全性和耐受性。次要目的：评价 RH119 在健康成年受试者中的免疫原性。探索性目的：探索不同免疫程序的 RH119 在健康成年受试者中的免疫原性。

Objectives of Study：

Main objective: To evaluate the safety and tolerability of RH119 in healthy adult subjects. Secondary objective: To evaluate the immunogenicity of RH119 in healthy adult subjects. Exploratory objective: To investigate the immunogenicity of RH119 with different immune programs in healthy adult subjects.

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

Inclusion criteria

1. Age range of 18-59 years old (including boundary values), gender not limited;
2. Agree to participate in this study and sign the informed consent form, comply with the requirements of the clinical research protocol, and complete the clinical study;
3. Subjects who have no history of tuberculosis in the past, and who have no clinical symptoms of active tuberculosis as judged by the researcher, and have no pathological changes consistent with active tuberculosis as confirmed by imaging, are excluded from mycobacterial tuberculosis infection by gamma interferon release test (IGRA) and tuberculin test (PPD);
4. Chest X-ray examination results show no abnormalities;
5. Vital sign examination (reference range for vital signs: systolic blood pressure 90~140mmHg, diastolic blood pressure 60~90mmHg, pulse 50~100 beats/minute, body temperature (axillary temperature)<37.3 ℃, physical examination, screening period clinical laboratory examination, other auxiliary examination results showing normal or abnormal without clinical significance judged by the researcher);
During the screening period, the CD4+T lymphocyte count should be >= 500 cells/μ L;
7. Female participants must meet the following criteria: surgical sterilization or postmenopausal for ≥ 2 years, or a negative pregnancy test for women of childbearing age (premenopausal or postmenopausal<2 years), and be willing to take effective contraceptive measures during the study period and within 12 months after full immunization (such as
Condoms are not allowed to be used alone with contraceptive pills.
8. Male participants must meet the following criteria: if they have not undergone sterilization surgery and have engaged in sexual activity that may lead to pregnancy, they agree to use effective contraceptive measures (such as condoms) during the study period and within 12 months after full immunization.

排除标准：

1. 既往有疫苗接种过敏史或对试验用药品任何成分过敏者； 2. 有已知或可疑（或有高危发生可能）的免疫功能损伤或异常者，如接受免疫抑制剂治疗（如长期应用全身糖皮质激素≥14 天，剂量≥2mg/kg/天或≥20mg/天泼尼松或相当于泼尼松剂量）者（不包括吸入性、关节内和局部类固醇用药）或免疫增强剂治疗者、在 3 个月内接受胃肠道以外的免疫球蛋白制剂或血液产品或血浆提取物者； 3. 急性发热性疾病、传染病（包括但不限于麻疹、百日咳、流行性感冒等）、有并发症的糖尿病、急性或渐进性肝病或肾病、急性眼结膜炎、急性中耳炎、严重心脏病、严重高血压、心肌损害、显著血管硬化、心内膜炎患者、恶性肿瘤患者等； 4. 有惊厥、癫痫、脑病（如先天性脑发育不全、脑外伤、脑肿瘤、脑出血、脑梗死、脑部感染、化学药物中毒等引起的大脑神经组织损伤等）和精神病等病史或精神病家族史者； 5. 无脾或功能性无脾，以及任何情况导致的无脾或脾切除者； 6. 活动性病毒性肝炎患者和/或人类免疫性缺陷病毒 HIV 抗体阳性和/或现患或既往患有梅毒者；原发或继发免疫功能受损或已被诊断为患有先天性或获得性免疫缺陷、淋巴瘤、白血病、系统性红斑狼疮（SLE）、类风湿性关节炎、幼年型类风湿性关节炎（JRA）、炎症性肠病或其他自身免疫疾病者； 7. 入组前 3 天内曾发热（腋温≥38.0℃），前 7 天内曾有需全身应用抗生素或抗病毒治疗的急性疾病或处于慢性感染急性期； 8. 处于哺乳期、孕期或在研究期间计划怀孕的女性，或在研究期间计划其伴侣受孕的男性； 9. 筛选前 3 个月内每周饮酒量大于 14 单位（1 单位= 17.7 mL 乙醇，即 1 单位 = 357 mL 酒精量为 5% 的啤酒或 43 mL 酒精量为 40% 的白酒或 147 mL 酒精量为 12% 的葡萄酒），或试验期间不能禁酒者； 10. 筛选前 6 个月内药物滥用史者； 11. 接种前 14 天内接受过任何疫苗或 28 天内接受过减毒活疫苗接种； 12. 首剂试验用疫苗接种前 3 个月内，参加过其他药物、医疗器械或疫苗临床试验； 13. 研究者认为受试者存在其他不适合参加本研究的情况，包括但不限于不能按研究方案参加随访或筛选期经研究者判断为健康状况不稳定的受试者等。

Exclusion criteria：

1. Individuals with a history of vaccine allergies or allergies to any component of the investigational drug; 2. Individuals with known or suspected (or high-risk) immune dysfunction or abnormalities, such as those receiving immunosuppressive therapy (such as long-term use of systemic corticosteroids for >= 14 days, dose >= 2mg/kg/day or >= 20mg/day of prednisone or equivalent prednisone dose) (excluding inhaled, intra-articular, and local steroid use) or immune enhancer therapy, and those receiving immunoglobulin preparations or blood products or plasma extracts outside the gastrointestinal tract within 3 months; 3. Acute febrile diseases, infectious diseases (including but not limited to measles, whooping cough, influenza, etc.), diabetes with complications, acute or progressive liver disease or kidney disease, acute conjunctivitis, acute otitis media, severe heart disease, severe hypertension, myocardial damage, significant vascular sclerosis, endocarditis, cancer patients, etc; 4. Individuals with a history of seizures, epilepsy, encephalopathy (such as congenital brain hypoplasia, traumatic brain injury, brain tumors, cerebral hemorrhage, cerebral infarction, brain infections, chemical drug poisoning, etc.), and psychiatric disorders or a family history of psychiatric disorders; 5. Patients with splenomegaly or functional splenomegaly, as well as those with splenomegaly or splenectomy caused by any circumstances; 6. Patients with active viral hepatitis and/or HIV antibody positive human immunodeficiency virus and/or current or previous syphilis; Individuals with primary or secondary immune dysfunction or diagnosed with congenital or acquired immunodeficiency, lymphoma, leukemia, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammatory bowel disease, or other autoimmune diseases; Within the first 3 days before enrollment, there was a fever (axillary temperature ≥ 38.0 ℃), and within the first 7 days, there was an acute disease requiring systemic antibiotic or antiviral treatment, or in the acute phase of chronic infection; 8. Women who are breastfeeding, pregnant, or planning to conceive during the study period, or men who plan to conceive their partners during the study period; 9. Those who drink more than 14 units (1 unit=17.7 mL ethanol, that is, 1 unit=357 mL beer with 5% alcohol, 43 mL Baijiu with 40% alcohol, or 147 mL wine with 12% alcohol) per week in the three months before screening, or cannot abstain from drinking during the test; 10. Screening for individuals with a history of drug abuse within the past 6 months; 11. Have received any vaccine within 14 days prior to vaccination or have received live attenuated vaccine within 28 days prior to vaccination; 12. Have participated in clinical trials of other drugs, medical devices, or vaccines within 3 months prior to the first dose of the trial vaccine; 13. The researchers believe that there are other circumstances in which the subjects are not suitable to participate in this study, including but not limited to those who cannot participate in follow-up according to the study protocol or those whose health status is deemed unstable by the researchers during the screening period.

研究实施时间：

Study execute time：

从 From 2024-12-12 00:00:00至 To 2026-06-30 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2024-12-16 00:00:00 至 To 2025-12-16 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	42
Group：	Treatment group	Sample size：	42
干预措施：	受试者将接受 50μg、100μg、125μg、150μg、200μg 和 250μg 六个剂量水平，免疫程序是间隔一个月接种两剂；在 100ug 剂量水平会额外探索免疫程序，免疫程序是间隔两个月接种两剂	干预措施代码：
Intervention：	The subjects will receive six dose levels of 50 μ g, 100 μ g, 125 μ g, 150 μ g, 200 μ g, and 250 μ g, with the immunization program consisting of two doses administered every month; At a dose level of 100ug, an additional immune program will be explored, which involves administering two doses every two months	Intervention code：

组别：	对照组	样本量：	14
Group：	Control group	Sample size：	14
干预措施：	安慰剂对照	干预措施代码：
Intervention：	Placebo control	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	湖北省	市(区县)：
Country：	China	Province：	Hubei	City：
单位(医院)：	武汉市金银潭医院(武汉市传染病医院)	单位级别：	三乙
Institution hospital：	Wuhan Jinyintan Hospital (Wuhan Infectious Disease Hospital)	Level of the institution：	Tertiary B

测量指标：

Outcomes：

指标中文名：	每剂 RH119 接种后 0-14 天征集性不良事件/不良反应发生率	指标类型：	主要指标
Outcome：	Collection of adverse events/reactions 0-14 days after each dose of RH119 vaccination	Type：	Primary indicator
测量时间点：	接种后 0-14	测量方法：
Measure time point of outcome：	0-14 days after vaccination	Measure method：

指标中文名：	每剂 RH119 接种后 0-28 天非征集性不良事件/不良反应发生率	指标类型：	主要指标
Outcome：	Collection of adverse events/reactions 0-28 days after each dose of RH119 vaccination	Type：	Primary indicator
测量时间点：	接种后 0-28 天	测量方法：
Measure time point of outcome：	0-28 days after vaccination	Measure method：

指标中文名：	末剂 RH119 接种至全程疫苗接种后 6 个月内 SAE、特别关注不良事件（Adverse Events of Special Interest，AESI）发生率	指标类型：	主要指标
Outcome：	The incidence of SAE and Adverse Events of Special Interest (AESI) within 6 months after the final dose of RH119 vaccination and the full course of vaccination	Type：	Primary indicator
测量时间点：	末剂 RH119 接种至全程疫苗接种后 6 个月内	测量方法：
Measure time point of outcome：	The final dose of RH119 should be administered within 6 months after the full course of vaccination	Measure method：

指标中文名：	实验室指标异常的发生情况和发生率	指标类型：	次要指标
Outcome：	The occurrence and rate of abnormal laboratory indicators in subjects	Type：	Secondary indicator
测量时间点：	受试者每剂接种后第 4 天	测量方法：
Measure time point of outcome：	on the 4th day after each dose of vaccination	Measure method：

指标中文名：	表达特异性细胞因子（IFN- γ、IL-2、TNF-α和 IL-4）的 CD4 + /CD8 + T 细胞比例	指标类型：	次要指标
Outcome：	The proportion of CD4+/CD8+T cells expressing specific cytokines (IFN - γ, IL-2, TNF - α, and IL-4)	Type：	Secondary indicator
测量时间点：	首剂疫苗接种前、首剂接种后第 14 天和第 30 天、第 2 剂接种前及接种后第 30 天、后 6 个月	测量方法：
Measure time point of outcome：	before the first dose of vaccine, on the 14th and 30th days after the first dose, before the second dose, on the 30th day after the second dose, and 6 months after the second dose	Measure method：

指标中文名：	RH119 的特异性抗体的表达水平	指标类型：	次要指标
Outcome：	The expression levels of RH119 specific antibodies	Type：	Secondary indicator
测量时间点：	首剂疫苗接种前、首剂接种后第 30 天、第 2 剂接种前及接种后第 30 天、后 6 个月，	测量方法：
Measure time point of outcome：	before the first dose of vaccine, on the 30th day after the first dose, before the second dose, and on the 30th day and 6 months after vaccination	Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	血液	组织：
Sample Name：	Blood	Tissue：
人体标本去向	使用后销毁	说明
Fate of sample：	Destruction after use	Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：

最小 Min age	18	岁 years
最大 Max age	59	岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

采用 SAS 9.4 或以上版本中的 PROC PLAN过程，除哨兵受试者外，其余受试者采用简单随机的方式按 2：1 的比例随机分配接种试验疫苗和安慰剂

Randomization Procedure (please state who generates the random number sequence and by what method)：

Using the PROC PLAN process in SAS 9.4 or above, except for sentinel subjects, all other subjects were randomly assigned to receive the trial vaccine and placebo in a 2:1 ratio using a simple randomization method

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法：	单盲，对受试者设盲。
Blinding：	Single blind, blinding the subjects.

是否共享原始数据： IPD sharing	否No
共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：	NA
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	NA
数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：	纸质版CRF
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	CRF
数据与安全监察委员会： Data and Safety Monitoring Committee：	暂未确定/Not yet
注册人： Name of Registration：	2024-12-16 17:14:12